Imaging Nociceptin Receptor Expression in Cannabis Use and Psychosis using Positron Emission Tomography with the radioligand [11C]NOP-1A
Bibliographic record
Abstract
Nociceptin/orphanin FQ (N/OFQ) is a neuropeptide transmitter in the brain that can suppress neurotransmitter release, including dopamine and glutamate. Therefore, dysregulation of nociceptin opioid peptide receptor (NOPr) signaling can result in neurotransmitter imbalance, suggesting its putative role in substance use disorder and psychosis. Furthermore, N/OFQ has been demonstrated to be involved in the brain’s stress response and in cognitive function. This study presents the first investigation of NOPr in these diseases using the highly specific ligand [11C]NOP-1A and positron emission tomography (PET). Study participants with long-term cannabis use and diagnosed as Clinical High Risk (CHR) and First Episode Psychosis (FEP) were included in the present work. The target regions of interest (ROI) include hippocampus, striatum, medial prefrontal cortex and dorsolateral prefrontal cortex. [11C]NOP-1A binding in the clinical groups was not significantly different compared to healthy volunteers. Cannabis users did not differ in [11C]NOP-1A binding from healthy volunteers and there were no significant group by ROI interactions. [11C]NOP-1A binding was not significantly different between FEP and healthy volunteers with no significant group by ROI interaction. [11C]NOP-1A binding was not significantly different between CHR and healthy volunteers with no significant group by ROI interaction. Interestingly, [11C]NOP-1A binding was associated with cognition in healthy volunteers. We report an interaction between group and immediate and delayed memory scores, such that as memory score increases, [11C]NOP-1A binding in the healthy volunteers decreases. This finding is line with preclinical animal studies that demonstrate N/OFQ agonist treatment or NOPr activation inhibits working memory abilities. In addition, [11C]NOP-1A binding is associated with self-reported stress in cannabis users and CHR. We report an interaction between group and chronic stress such that as stress score increases, [11C]NOP-1A binding in the cannabis users and CHR decreases, but increases in HV. This finding is line with studies that have demonstrated that stress mobilizes the nociceptin receptor system. Our results suggest that cannabis users and CHR patients, which are known to have abnormal stress responses, are unable to upregulate NOPr to counteract stress. Therefore, this may suggest NOPr as a novel target for interventions in these populations.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".